Ablation of α ₂ δ-1 inhibits cell-surface trafficking of endogenous N-type calcium channels in the pain pathway in vivo

Significance Neuronal N-type (Ca V 2.2) voltage-gated calcium channels are important at the first synapse in the pain pathway. In this study, we have characterized a knockin mouse containing Ca V 2.2 with an extracellular HA tag to determine the localization of Ca V 2.2 in primary afferent pain pathways. These endogenous channels have been visualized at the plasma membrane and rigorously quantified in vivo. We examined the effect of ablation of the calcium channel auxiliary subunit α 2 δ-1 (the target of gabapentinoids) on Ca V 2.2 distribution. We found preferential cell-surface localization of Ca V 2.2 in DRG nociceptor neuron cell bodies was lost, accompanied by a dramatic reduction at dorsal horn terminals, but no effect on distribution of other spinal cord synaptic markers.